Your Digest for Wednesday, Jan 31, 2024 02:59 PM


[!INFO] Aspirin prophylaxis
"Women who are at high risk of developing pre-eclampsia should take aspirin 75mg od from 12 weeks until the birth of the baby." - NICE via Passmedicine

Pathogensis of pregnancy associated hypertensive disorders

Current research demonstrates that improper trophoblast differentiation during endothelial invasion due to abnormal regulation and/or production of cytokines, adhesion molecules, major histocompatibility complex molecules, and metalloproteinases plays a key role in the development of a gestational hypertensive disease.  Abnormal regulation and/or production of these molecules leads to abnormal development and remodeling of spiral arteries in the deep myometrial tissues. This leads to placental hypoperfusion and ischemia. More recent research shows role of antiangiogenic factors that are released by placental tissue cause SYSTEMIC ENDOTHELIAL DYSFUNCTION which can result in systemic hypertension. (in PIH, activity of angiogenic factors like VEGF and PlGF - placental growth factor - are reduced) Organ hypoperfusion from endothelial dysfunction is most commonly seen in the eyes, lungs, liver, kidneys and peripheral vasculature. Overall, most experts agree underlying reason is multifactorial

Medical management of PIH


[!TIP] mnemonic: 'flozins' are SGLT-2 inhibitors
Glucose 'flowz in' the PCT

General properties of hypoglycaemic agents

Protective effects of hypoglycemic agents

OralHypoglycemicMedicationBenefitsCVD.png
Source

Evidence on protective effects of hypoglycemic agents

oralHypoglycemicsBenefitsEvidence.pngSource

Indications for selecting a hypoglycemic agent

indicationsForSpecificHypoglycemicAgents.png
| Agent | Class | Mechanism | Side effects | Other stuff | Expected effect |
| ------------------------------------------------ | -------------------------------- | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------- |
| Metformin | Biguanide | Insulin sensitiztion Reduce hepatic gluconeogenesis. | GI side effects Lactic acidosis (risk in renal/liver/heart failure – contrindications) No weight gain May reduce apetite, STOP when eGFR < 30 | Reduced GI B12 absorption The usual first line agent, can be combined with other | Lower FBS by about 50 mg/dL Lowers HbA1C by about 1% |
| Pioglitazone is the only one | Thiazolidinediones (glitazones) | Increases insulin sensitivity by binding nuclear receptors and altering gene expression may increase glucose consumption in muscle cells | no hypoglycaemia Commonly weight gain Fluid retention → precipitates Heart failure | May specifically benefit NAFLD | take up to 3 months to reach maximal effect. |
| Gliclazide Glimipiride Glibenclamide Tolbutamide | Sulphonylureas | Promotes depolarization of beta cell → stimulates insulin secretion (by binding ATP dependent k+ channel) | Weight gain! Hypoglycaemia | Effect will wear off with age as beta cell mass declines Risk of hypoglycaemia increases with age and intercurrent infection and duration of drug action Gliclazide / Glipizide / tolbutamide → Short acting Glimiperide → ? long acting but lower hypo risk Glyburide(= Glibenclamide) – long acting | Similar to metformin Weight gain of 1-4 Kg |
| Repaglinide | Meglitinides ("slp.ureas lite") | Post prandial insulin releasers (binds ATP dependent k+ channel like sulfonylureas) but act only for 3 hrs. So effective only in post prandial period when taken with meals | Hypoglycaemia Weight gain (but less than s.ureas) | Taken about 30 minutes before meals. | Less effective than other drugs. Role in DM Mx is not clear. Can be used with metformin is C/I or when patient only has post prandial hyperglycaemia |
| Sitagliptin Linigliptin | DPP-4 inhibitors (gliptins) | Inhibit GLP-1 breakdown (restore physiologic GLP levels) → promotion of insulin secretion GLP1 receptors are also found in the cardiovascular system | Good S/E profile. | Used as second line drug, in early DM when insulin secretion is still preserved. Combined with metformin / sulfonylurea | Modest effect but used because of low S/E profile. |
| Empagliflozin Dapagliflozin Canagliflozin | SGLT inhibitors | Inhibit the coupled reabsorption of sodium and glucose from the proximal tubules (+ other renal effects) | Dehydration Genital candidiasis (but not bacterial UTI),Can precipitate DKA (increase production of ketones) | Wonder drug! Decreases weight Improve renal dysfuntion – renoprotective Reduce atherosclerotic events! Reduce risk of heart failure | ?More potent glucose lowering than metformin(values given in K&C). Weight loss of 2-4 Kg over 1 year |
| GLP - Agonists - See Below | | | | | |
| | | | | | |


- *GI symptoms*

extrapulmonary manifestations:

Diagnosis: fastidious organism, use PCR

cyclosporaCayatensis.png


[!INFO] Ergot Vs. Non Ergot antiparkinson medications: Fibrosis Vs Non fibrotic

[!TIP] Mnemonic: Dopamine agonists

Ergot derived NON ergot
Fungal PeLiCan B PramOnRottinRope
Pergolide, Lisuride, Cabergoline, Bromocriptine pramipexole, ropinirole, rotigotine
  - Common Side effect of levodopa and dopamine agonists. Can be due to *inadequate* DDC inhibitor. *Treat with domperidone* but *avoid metoclopramide* which *crosses the BBB*. Early side effect. Settles with time.

shortcuts to select antiparkinson's drugs

Apparently these tables were created by NICE. Found on Passmedicine.

Effect Levodopa
Dopamine agonists
MAO‑B inhibitors
Motor symptoms More improvement in motor symptoms Less improvement in motor symptoms Less improvement in motor symptoms
Activities of daily living More improvement in activities of daily living Less improvement in activities of daily living Less improvement in activities of daily living
Motor complications More motor complications Fewer motor complications Fewer motor complications
Adverse events Fewer specified adverse events* More specified adverse events* Fewer specified adverse events*
* side effects : excessive sleepiness, hallucinations and impulse control disorders

"If a patient continues to have symptoms despite optimal levodopa treatment or has developed dyskinesia then NICE recommend the addition of a dopamine agonist, MAO‑B inhibitor or catechol‑O‑methyl transferase (COMT) inhibitor as an adjunct. Again, NICE summarise the main points in terms of decision making:"

Effect Dopamine agonists MAO‑B inhibitors COMT inhibitors Amantadine
Motor symptoms Improvement in motor symptoms Improvement in motor symptoms Improvement in motor symptoms No evidence of improvement in motor symptoms
Activities of daily living Improvement in activities of daily living Improvement in activities of daily living Improvement in activities of daily living No evidence of improvement in activities of daily living
Off time More off‑time reduction Off‑time reduction Off‑time reduction No studies reporting this outcome
Adverse events Intermediate risk of adverse events Fewer adverse events More adverse events No studies reporting this outcome
Hallucinations More risk of hallucinations Lower risk of hallucinations Lower risk of hallucinations No studies reporting this outcome

And of course, my own table.
| Entacapone | Catachol-O-methyltransferase inhibitor (prevents peripheral degradation of levodopa) | Prolongs levodopa action - used to manage on/off phenomena + end of dose 'wearing off'; often combined with levodopa | Gastrointestinal and dyskinetic side effects |


  1. Humans can get infected by

[!INFO] See [[#Comparison of amoebiasis and giardiasis]] below

Comparison of amoebiasis and giardiasis

Amoebiasis Giardiasis Cyclosporiasis
Protozoan Protozoan
Cyst is infective Cyst is infective
Cysts survive in environment Cysts survive in environment
faeco-oral transmission Faeco-oral transmission
Cysts resistant to gastric acid Cyst resistant to chlorine
Trophozoites cause disease Same
Invasive Usually not invasive Sporozoites invade small intestinal epithelial cells
Trophozoites localize in large intestine Small intestine Small intestine
Cyst ?immediately infective Cyst immediately infective Cyst must mature for days to weeks in environment -> human to human transmission unlikely.
Metronidazole / paromoycin Tinidazole / metro TMP + SMX

  1. Patient is clinically well.